JP2834577B2 - 抗不安作用を有するピペリジン誘導体 - Google Patents
抗不安作用を有するピペリジン誘導体Info
- Publication number
- JP2834577B2 JP2834577B2 JP5500747A JP50074792A JP2834577B2 JP 2834577 B2 JP2834577 B2 JP 2834577B2 JP 5500747 A JP5500747 A JP 5500747A JP 50074792 A JP50074792 A JP 50074792A JP 2834577 B2 JP2834577 B2 JP 2834577B2
- Authority
- JP
- Japan
- Prior art keywords
- piperidine
- spiro
- isobenzofuran
- butyl
- sup
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 230000000949 anxiolytic effect Effects 0.000 title abstract description 8
- 150000003053 piperidines Chemical class 0.000 title abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 5
- 206010010904 Convulsion Diseases 0.000 claims abstract description 5
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 5
- 206010015037 epilepsy Diseases 0.000 claims abstract description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 5
- 208000000044 Amnesia Diseases 0.000 claims abstract description 4
- 208000031091 Amnestic disease Diseases 0.000 claims abstract description 4
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 4
- 208000016285 Movement disease Diseases 0.000 claims abstract description 4
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 4
- 230000006986 amnesia Effects 0.000 claims abstract description 4
- 230000036506 anxiety Effects 0.000 claims abstract description 4
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000005977 Ethylene Substances 0.000 claims abstract description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 6
- 150000001875 compounds Chemical class 0.000 claims description 119
- BYOIMOJOKVUNTP-UHFFFAOYSA-N spiro[1h-2-benzofuran-3,4'-piperidine] Chemical compound C12=CC=CC=C2COC21CCNCC2 BYOIMOJOKVUNTP-UHFFFAOYSA-N 0.000 claims description 98
- -1 2-thiazolyl Chemical group 0.000 claims description 95
- 238000000034 method Methods 0.000 claims description 90
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 43
- 125000003003 spiro group Chemical group 0.000 claims description 28
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 208000020016 psychiatric disease Diseases 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- SJKXTDDOYIWJMH-UHFFFAOYSA-N 1'-[4-[1-(4-fluorophenyl)indol-3-yl]butyl]spiro[1,4-dihydroisochromene-3,4'-piperidine] Chemical compound C1=CC(F)=CC=C1N1C2=CC=CC=C2C(CCCCN2CCC3(CC2)OCC2=CC=CC=C2C3)=C1 SJKXTDDOYIWJMH-UHFFFAOYSA-N 0.000 claims 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 108010085082 sigma receptors Proteins 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
- 238000010171 animal model Methods 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- 230000036461 convulsion Effects 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 121
- 230000008018 melting Effects 0.000 description 121
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 115
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 100
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
- 239000003921 oil Substances 0.000 description 71
- 235000019198 oils Nutrition 0.000 description 71
- 230000002829 reductive effect Effects 0.000 description 70
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 52
- 239000000203 mixture Substances 0.000 description 50
- 239000002904 solvent Substances 0.000 description 49
- 239000000243 solution Substances 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000003480 eluent Substances 0.000 description 21
- 238000001035 drying Methods 0.000 description 20
- 239000012280 lithium aluminium hydride Substances 0.000 description 20
- LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 15
- 150000003891 oxalate salts Chemical class 0.000 description 15
- 235000006408 oxalic acid Nutrition 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 238000012360 testing method Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 10
- 239000003982 sigma receptor ligand Substances 0.000 description 10
- 238000009739 binding Methods 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 239000007983 Tris buffer Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- 125000005605 benzo group Chemical group 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000011976 maleic acid Substances 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 230000036515 potency Effects 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000002168 alkylating agent Substances 0.000 description 6
- 229940100198 alkylating agent Drugs 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 229960003638 dopamine Drugs 0.000 description 5
- 150000007857 hydrazones Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- OPNUROKCUBTKLF-UHFFFAOYSA-N 1,2-bis(2-methylphenyl)guanidine Chemical compound CC1=CC=CC=C1N\C(N)=N\C1=CC=CC=C1C OPNUROKCUBTKLF-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NTCVORQAIAUAJB-UHFFFAOYSA-N [Mg].[W] Chemical compound [Mg].[W] NTCVORQAIAUAJB-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000001530 fumaric acid Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- QNXSIUBBGPHDDE-UHFFFAOYSA-N indan-1-one Chemical compound C1=CC=C2C(=O)CCC2=C1 QNXSIUBBGPHDDE-UHFFFAOYSA-N 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical class CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- GUDVQJXODNJRIJ-CALCHBBNSA-N 9-[3-[(3S,5R)-3,5-dimethyl-1-piperazinyl]propyl]carbazole Chemical compound C1[C@@H](C)N[C@@H](C)CN1CCCN1C2=CC=CC=C2C2=CC=CC=C21 GUDVQJXODNJRIJ-CALCHBBNSA-N 0.000 description 3
- 108060003345 Adrenergic Receptor Proteins 0.000 description 3
- 102000017910 Adrenergic receptor Human genes 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 150000002688 maleic acid derivatives Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 229920001592 potato starch Polymers 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229950004933 rimcazole Drugs 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- QVKNICXDNWDLFN-UHFFFAOYSA-N spiro[1,3-benzodioxole-2,4'-piperidine] Chemical compound C1CNCCC21OC1=CC=CC=C1O2 QVKNICXDNWDLFN-UHFFFAOYSA-N 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 239000003039 volatile agent Substances 0.000 description 3
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- ZXUYYZPJUGQHLQ-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanol Chemical compound C=1C=C(F)C=CC=1C(O)CCCN(CC1)CCN1C1=NC=C(F)C=N1 ZXUYYZPJUGQHLQ-UHFFFAOYSA-N 0.000 description 2
- OUMVYPXVYMLOIC-UHFFFAOYSA-N 1-[2-chloro-5-(trifluoromethyl)phenyl]-5-hydroxypentan-1-one Chemical compound OCCCCC(=O)C1=CC(C(F)(F)F)=CC=C1Cl OUMVYPXVYMLOIC-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- ADHAJDDBRUOZHJ-UHFFFAOYSA-N 1-benzothiophen-3-one Chemical compound C1=CC=C2C(=O)CSC2=C1 ADHAJDDBRUOZHJ-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- 229940044613 1-propanol Drugs 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- WGABOZPQOOZAOI-UHFFFAOYSA-N 2-[4-[[(3,5-dimethoxy-4-methylbenzoyl)-(3-phenylpropyl)amino]methyl]phenyl]acetic acid Chemical compound COC1=C(C)C(OC)=CC(C(=O)N(CCCC=2C=CC=CC=2)CC=2C=CC(CC(O)=O)=CC=2)=C1 WGABOZPQOOZAOI-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- LKSXLNMBLGXHQS-UHFFFAOYSA-N 3-(4-fluorophenyl)-8-azabicyclo[3.2.1]oct-3-ene Chemical compound C1=CC(F)=CC=C1C(C1)=CC2NC1CC2 LKSXLNMBLGXHQS-UHFFFAOYSA-N 0.000 description 2
- XNXGLTJWOZMRNZ-UHFFFAOYSA-N 3-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane Chemical compound C1=CC(F)=CC=C1C1CC(N2)CCC2C1 XNXGLTJWOZMRNZ-UHFFFAOYSA-N 0.000 description 2
- HERUOVVKVXUUKK-UHFFFAOYSA-N 3-(5-fluoro-1-benzofuran-3-yl)propan-1-ol Chemical compound C1=C(F)C=C2C(CCCO)=COC2=C1 HERUOVVKVXUUKK-UHFFFAOYSA-N 0.000 description 2
- QBFBBLJMOZRSBU-UHFFFAOYSA-N 3-(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)propan-1-ol Chemical compound C1=C(F)C=C2C(CCCO)COC2=C1 QBFBBLJMOZRSBU-UHFFFAOYSA-N 0.000 description 2
- LQIHNVZYUXEWAQ-UHFFFAOYSA-N 3-(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)propanoic acid Chemical compound C1=C(F)C=C2C(CCC(=O)O)COC2=C1 LQIHNVZYUXEWAQ-UHFFFAOYSA-N 0.000 description 2
- OOEBMSIXFBAKMV-UHFFFAOYSA-N 4-(2,3-dihydro-1h-inden-1-yl)but-3-en-1-ol Chemical compound C1=CC=C2C(C=CCCO)CCC2=C1 OOEBMSIXFBAKMV-UHFFFAOYSA-N 0.000 description 2
- NBWKZEUULFAUHU-UHFFFAOYSA-N 4-(5-fluoro-1-benzofuran-3-yl)butanoic acid Chemical compound C1=C(F)C=C2C(CCCC(=O)O)=COC2=C1 NBWKZEUULFAUHU-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- VUEQAXHGKCKXFV-UHFFFAOYSA-N 4-phenylbutyl methanesulfonate Chemical compound CS(=O)(=O)OCCCCC1=CC=CC=C1 VUEQAXHGKCKXFV-UHFFFAOYSA-N 0.000 description 2
- PAVTXINZFWRQOD-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1-benzofuran Chemical compound FC1=CC=C2OCCC2=C1 PAVTXINZFWRQOD-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- 208000014094 Dystonic disease Diseases 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000019430 Motor disease Diseases 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 229940008309 acetone / ethanol Drugs 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000006254 arylation reaction Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
- 229940126212 compound 17a Drugs 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical compound C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 229940087646 methanolamine Drugs 0.000 description 2
- RWIKCBHOVNDESJ-NSCUHMNNSA-N methyl (e)-4-bromobut-2-enoate Chemical compound COC(=O)\C=C\CBr RWIKCBHOVNDESJ-NSCUHMNNSA-N 0.000 description 2
- FSJAXBXCHWMNAB-UHFFFAOYSA-N methyl 1-benzothiophene-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CSC2=C1 FSJAXBXCHWMNAB-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- PLWMBYBVKVUTBR-UHFFFAOYSA-N spiro[2,3-dihydro-1h-naphthalene-4,4'-piperidine] Chemical compound C1CCC2=CC=CC=C2C21CCNCC2 PLWMBYBVKVUTBR-UHFFFAOYSA-N 0.000 description 2
- 238000011272 standard treatment Methods 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000005694 sulfonylation reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- RUSDDKCNWDTJPN-UHFFFAOYSA-N (1-phenylindol-3-yl) acetate Chemical compound C12=CC=CC=C2C(OC(=O)C)=CN1C1=CC=CC=C1 RUSDDKCNWDTJPN-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- AEVBPXDFDKBGLT-YOUFYPILSA-N (2s,3s,4r,5r)-n-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1NC(=O)CNC(=O)[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 AEVBPXDFDKBGLT-YOUFYPILSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- CIWZXJOBXQEOJK-UHFFFAOYSA-N (5-fluoro-2,3-dihydro-1-benzofuran-3-yl)methanol Chemical compound C1=C(F)C=C2C(CO)COC2=C1 CIWZXJOBXQEOJK-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- RHYXMPHVBWGZLR-UHFFFAOYSA-N 1'-(3-phenoxypropyl)spiro[1H-2-benzofuran-3,4'-piperidine] Chemical compound C1CC2(C3=CC=CC=C3CO2)CCN1CCCOC1=CC=CC=C1 RHYXMPHVBWGZLR-UHFFFAOYSA-N 0.000 description 1
- PSTUTYYRXRFYBI-UHFFFAOYSA-N 1'-(4-phenylbutyl)spiro[1,2-dihydroindene-3,4'-piperidine] Chemical compound C1CC2(C3=CC=CC=C3CC2)CCN1CCCCC1=CC=CC=C1 PSTUTYYRXRFYBI-UHFFFAOYSA-N 0.000 description 1
- IPPARLPUDOUUJH-UHFFFAOYSA-N 1'-(4-phenylbutyl)spiro[1,3-benzodioxole-2,4'-piperidine] Chemical compound C1CC2(OC3=CC=CC=C3O2)CCN1CCCCC1=CC=CC=C1 IPPARLPUDOUUJH-UHFFFAOYSA-N 0.000 description 1
- PMFUDZXSLUFGKX-UHFFFAOYSA-N 1'-(4-phenylbutyl)spiro[1,4-dihydroisochromene-3,4'-piperidine] Chemical compound C1CC2(OCC3=CC=CC=C3C2)CCN1CCCCC1=CC=CC=C1 PMFUDZXSLUFGKX-UHFFFAOYSA-N 0.000 description 1
- SKACYGUTKUPQBQ-UHFFFAOYSA-N 1'-(4-phenylbutyl)spiro[3,4-dihydrochromene-2,4'-piperidine] Chemical compound C1CC2(OC3=CC=CC=C3CC2)CCN1CCCCC1=CC=CC=C1 SKACYGUTKUPQBQ-UHFFFAOYSA-N 0.000 description 1
- MUJCPZIOPHMDMH-UHFFFAOYSA-N 1'-(4-phenylbutyl)spiro[chromene-2,4'-piperidine] Chemical compound C1CC2(C=CC3=CC=CC=C3O2)CCN1CCCCC1=CC=CC=C1 MUJCPZIOPHMDMH-UHFFFAOYSA-N 0.000 description 1
- QMTVKPIRPXBNQW-UHFFFAOYSA-N 1'-[3-(1-adamantyloxy)propyl]spiro[isochromene-3,4'-piperidine] Chemical compound O1C=C2C=CC=CC2=CC1(CC1)CCN1CCCOC1(C2)CC(C3)CC2CC3C1 QMTVKPIRPXBNQW-UHFFFAOYSA-N 0.000 description 1
- SEJJECIQLYCFOZ-UHFFFAOYSA-N 1'-[4-(1-benzothiophen-3-yl)butyl]spiro[1,4-dihydroisochromene-3,4'-piperidine] Chemical compound C1C2=CC=CC=C2COC1(CC1)CCN1CCCCC1=CSC2=CC=CC=C12 SEJJECIQLYCFOZ-UHFFFAOYSA-N 0.000 description 1
- CGWOWVAKPOLARM-UHFFFAOYSA-N 1'-[4-(1h-indol-3-yl)butyl]spiro[1,3-benzodioxole-2,4'-piperidine] Chemical compound O1C2=CC=CC=C2OC1(CC1)CCN1CCCCC1=CNC2=CC=CC=C12 CGWOWVAKPOLARM-UHFFFAOYSA-N 0.000 description 1
- VUFUIDNKBYKSMC-UHFFFAOYSA-N 1'-[4-[1-(4-fluorophenyl)indol-3-yl]butyl]spiro[2,3-dihydrochromene-4,4'-piperidine] Chemical compound C1=CC(F)=CC=C1N1C2=CC=CC=C2C(CCCCN2CCC3(C4=CC=CC=C4OCC3)CC2)=C1 VUFUIDNKBYKSMC-UHFFFAOYSA-N 0.000 description 1
- RORQUKGUCNRPOX-UHFFFAOYSA-N 1'-benzylspiro[1h-naphthalene-4,4'-piperidine] Chemical compound C1CC2(C3=CC=CC=C3CC=C2)CCN1CC1=CC=CC=C1 RORQUKGUCNRPOX-UHFFFAOYSA-N 0.000 description 1
- YNMVLXLZUYHTJZ-UHFFFAOYSA-N 1'-benzylspiro[chromene-2,4'-piperidine] Chemical compound C1CC2(C=CC3=CC=CC=C3O2)CCN1CC1=CC=CC=C1 YNMVLXLZUYHTJZ-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 1
- JUXAVSAMVBLDKO-UHFFFAOYSA-N 1-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(1h-indol-3-yl)-1-oxo-1-spiro[1,2-dihydroindene-3,4'-piperidine]-1'-ylpropan-2-yl]urea Chemical class C1N(CC2)CCC2C1NC(=O)NC(C(=O)N1CCC2(C3=CC=CC=C3CC2)CC1)CC1=CNC2=CC=CC=C12 JUXAVSAMVBLDKO-UHFFFAOYSA-N 0.000 description 1
- GJIZPJUNZBYIDB-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-(4-phenylpiperidin-1-yl)butyl]indole Chemical compound C1=CC(F)=CC=C1N1C2=CC=CC=C2C(CCCCN2CCC(CC2)C=2C=CC=CC=2)=C1 GJIZPJUNZBYIDB-UHFFFAOYSA-N 0.000 description 1
- NRZHEKZOMMPQDG-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[3-(4-fluorophenyl)-8-azabicyclo[3.2.1]oct-3-en-8-yl]butyl]indole Chemical compound C1=CC(F)=CC=C1C(C1)=CC2N(CCCCC=3C4=CC=CC=C4N(C=4C=CC(F)=CC=4)C=3)C1CC2 NRZHEKZOMMPQDG-UHFFFAOYSA-N 0.000 description 1
- NGVLXUDHOKGWPG-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[4-(4-fluorophenyl)piperidin-1-yl]butyl]indole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCC=2C3=CC=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 NGVLXUDHOKGWPG-UHFFFAOYSA-N 0.000 description 1
- FPSNEPLNXKCSKH-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[4-(4-methylphenyl)piperidin-1-yl]butyl]indole Chemical compound C1=CC(C)=CC=C1C1CCN(CCCCC=2C3=CC=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 FPSNEPLNXKCSKH-UHFFFAOYSA-N 0.000 description 1
- GLGMGEWPXJFMBW-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]butyl]indole Chemical compound C1=CC(F)=CC=C1N1C2=CC=CC=C2C(CCCCN2CCC(CC2)C=2C=C(C=CC=2)C(F)(F)F)=C1 GLGMGEWPXJFMBW-UHFFFAOYSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- UYGMKSKKGSUAHB-UHFFFAOYSA-N 1-benzothiophen-3-ylmethanol Chemical compound C1=CC=C2C(CO)=CSC2=C1 UYGMKSKKGSUAHB-UHFFFAOYSA-N 0.000 description 1
- FRJNKYGTHPUSJR-UHFFFAOYSA-N 1-benzothiophene 1,1-dioxide Chemical class C1=CC=C2S(=O)(=O)C=CC2=C1 FRJNKYGTHPUSJR-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- DXFLXXYSOGECDN-UHFFFAOYSA-N 1h-indol-2-yl acetate Chemical compound C1=CC=C2NC(OC(=O)C)=CC2=C1 DXFLXXYSOGECDN-UHFFFAOYSA-N 0.000 description 1
- HKTRXNIXBBRAHO-UHFFFAOYSA-N 2,2,2-trichloroethyl 3-(4-fluorophenyl)-8-azabicyclo[3.2.1]oct-3-ene-8-carboxylate Chemical compound C1=CC(F)=CC=C1C(C1)=CC2N(C(=O)OCC(Cl)(Cl)Cl)C1CC2 HKTRXNIXBBRAHO-UHFFFAOYSA-N 0.000 description 1
- CTTGZEDHPSNKQT-UHFFFAOYSA-N 2,2,2-trichloroethyl 5-(4-fluorophenyl)-8-azabicyclo[3.2.1]oct-3-ene-8-carboxylate Chemical compound C1=CC(F)=CC=C1C1(N2C(=O)OCC(Cl)(Cl)Cl)C=CCC2CC1 CTTGZEDHPSNKQT-UHFFFAOYSA-N 0.000 description 1
- YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical compound C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 1
- BVSIAYQIMUUCRW-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=NOC2=C1 BVSIAYQIMUUCRW-UHFFFAOYSA-N 0.000 description 1
- CYKKOJQAYUCNGO-UHFFFAOYSA-N 2-(1,2-benzoxazol-3-yl)ethanol Chemical compound C1=CC=C2C(CCO)=NOC2=C1 CYKKOJQAYUCNGO-UHFFFAOYSA-N 0.000 description 1
- HCYFGRCYSCXKNQ-UHFFFAOYSA-N 2-(1,3-dimethyl-2,6-dioxo-7-purinyl)acetic acid Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)=O)C=N2 HCYFGRCYSCXKNQ-UHFFFAOYSA-N 0.000 description 1
- NFEXPXKLJWPVAT-UHFFFAOYSA-N 2-(1-benzothiophen-3-ylmethoxy)ethanol Chemical compound C1=CC=C2C(COCCO)=CSC2=C1 NFEXPXKLJWPVAT-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ULLKKVHOLFDNFB-UHFFFAOYSA-N 2-[3-(4-hydroxybutyl)indol-1-yl]-n,n-dimethylacetamide Chemical compound C1=CC=C2N(CC(=O)N(C)C)C=C(CCCCO)C2=C1 ULLKKVHOLFDNFB-UHFFFAOYSA-N 0.000 description 1
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- KWWHFBHPKIUFMP-UHFFFAOYSA-N 2-[5-chloro-1-(4-fluorophenyl)indol-3-yl]oxyacetic acid Chemical compound C12=CC=C(Cl)C=C2C(OCC(=O)O)=CN1C1=CC=C(F)C=C1 KWWHFBHPKIUFMP-UHFFFAOYSA-N 0.000 description 1
- HYPPFDDKLRFGCC-UHFFFAOYSA-N 2-[5-chloro-1-(4-fluorophenyl)indol-3-yl]oxyethyl methanesulfonate Chemical compound C12=CC=C(Cl)C=C2C(OCCOS(=O)(=O)C)=CN1C1=CC=C(F)C=C1 HYPPFDDKLRFGCC-UHFFFAOYSA-N 0.000 description 1
- GEHMLBFNZKJDQM-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=C(C#N)C(Cl)=C1 GEHMLBFNZKJDQM-UHFFFAOYSA-N 0.000 description 1
- XBPPLECAZBTMMK-UHFFFAOYSA-N 2-chloro-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CCl XBPPLECAZBTMMK-UHFFFAOYSA-N 0.000 description 1
- BKFSUZNMFPCJNJ-UHFFFAOYSA-N 2-hydroxy-3,4-dimethylidenecyclohexa-1,5-diene-1-carboxylic acid Chemical compound OC(=O)C=1C=CC(=C)C(=C)C=1O BKFSUZNMFPCJNJ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- UVECZJOMLAWTEK-UHFFFAOYSA-N 3-(1,2-benzoxazol-3-yl)propanenitrile Chemical compound C1=CC=C2C(CCC#N)=NOC2=C1 UVECZJOMLAWTEK-UHFFFAOYSA-N 0.000 description 1
- LLCUDRDRIOYTEI-UHFFFAOYSA-N 3-(1-benzothiophen-3-yloxy)propan-1-ol Chemical compound C1=CC=C2C(OCCCO)=CSC2=C1 LLCUDRDRIOYTEI-UHFFFAOYSA-N 0.000 description 1
- HEVCXANBEHDQBH-UHFFFAOYSA-N 3-(1-benzothiophen-3-ylsulfanyl)propanoic acid Chemical compound C1=CC=C2C(SCCC(=O)O)=CSC2=C1 HEVCXANBEHDQBH-UHFFFAOYSA-N 0.000 description 1
- VUVTVEOGOFEBKR-UHFFFAOYSA-N 3-(2-chloroethyl)-1-benzothiophene Chemical compound C1=CC=C2C(CCCl)=CSC2=C1 VUVTVEOGOFEBKR-UHFFFAOYSA-N 0.000 description 1
- PBSIHSPJXGVELM-UHFFFAOYSA-N 3-(5-fluoro-1-benzofuran-3-yl)propanoic acid Chemical compound C1=C(F)C=C2C(CCC(=O)O)=COC2=C1 PBSIHSPJXGVELM-UHFFFAOYSA-N 0.000 description 1
- FJDUBXIMFKKOPV-UHFFFAOYSA-N 3-(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)propyl methanesulfonate Chemical compound C1=C(F)C=C2C(CCCOS(=O)(=O)C)COC2=C1 FJDUBXIMFKKOPV-UHFFFAOYSA-N 0.000 description 1
- MTEMZLYNDSLNST-UHFFFAOYSA-N 3-[3-[4-(4-fluorophenyl)piperidin-1-yl]propoxy]-1,2-benzothiazole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCOC=2C3=CC=CC=C3SN=2)CC1 MTEMZLYNDSLNST-UHFFFAOYSA-N 0.000 description 1
- DYRMKCCGPIZVMM-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)piperidin-1-yl]propan-1-ol Chemical compound C1CN(CCCO)CCC1C1=CC=C(F)C=C1 DYRMKCCGPIZVMM-UHFFFAOYSA-N 0.000 description 1
- JHLJHQQFPBTTJE-UHFFFAOYSA-N 3-[4-(4-phenylpiperidin-1-yl)butyl]-1h-indole Chemical compound C=1NC2=CC=CC=C2C=1CCCCN(CC1)CCC1C1=CC=CC=C1 JHLJHQQFPBTTJE-UHFFFAOYSA-N 0.000 description 1
- OKQALJBWMOZBSK-UHFFFAOYSA-N 3-[4-[3-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-8-yl]butyl]-1,2-benzoxazole Chemical compound C1=CC(F)=CC=C1C1CC(N2CCCCC=3C4=CC=CC=C4ON=3)CCC2C1 OKQALJBWMOZBSK-UHFFFAOYSA-N 0.000 description 1
- OVTHWSXLADCZIL-UHFFFAOYSA-N 3-[4-[4-(2,6-dichlorophenyl)piperidin-1-yl]butyl]-1,2-benzoxazole Chemical compound ClC1=CC=CC(Cl)=C1C1CCN(CCCCC=2C3=CC=CC=C3ON=2)CC1 OVTHWSXLADCZIL-UHFFFAOYSA-N 0.000 description 1
- GNKWZQFMKSMGEV-UHFFFAOYSA-N 3-[4-[4-(2-methoxyphenyl)piperidin-1-yl]butyl]-2,3-dihydro-1h-indole Chemical compound COC1=CC=CC=C1C1CCN(CCCCC2C3=CC=CC=C3NC2)CC1 GNKWZQFMKSMGEV-UHFFFAOYSA-N 0.000 description 1
- VDVHMPOFBZDIPT-UHFFFAOYSA-N 3-[4-[4-(3,4-dichlorophenyl)piperidin-1-yl]butyl]-1h-indole Chemical compound C1=C(Cl)C(Cl)=CC=C1C1CCN(CCCCC=2C3=CC=CC=C3NC=2)CC1 VDVHMPOFBZDIPT-UHFFFAOYSA-N 0.000 description 1
- QLVPKVJVNZJRMP-UHFFFAOYSA-N 3-[4-[4-(4-fluorophenyl)piperidin-1-yl]butyl]-1,2-benzoxazole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCC=2C3=CC=CC=C3ON=2)CC1 QLVPKVJVNZJRMP-UHFFFAOYSA-N 0.000 description 1
- ODHNCRXSTVFKDW-UHFFFAOYSA-N 3-[4-[4-(4-fluorophenyl)piperidin-1-yl]butyl]-1-phenylindole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCC=2C3=CC=CC=C3N(C=3C=CC=CC=3)C=2)CC1 ODHNCRXSTVFKDW-UHFFFAOYSA-N 0.000 description 1
- IWKGLMYMNLYLTK-UHFFFAOYSA-N 3-[6-[4-(4-fluorophenyl)piperidin-1-yl]hexyl]-1h-indole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCCCC=2C3=CC=CC=C3NC=2)CC1 IWKGLMYMNLYLTK-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- LNGXBZDOEJQTMR-UHFFFAOYSA-N 4-(1,2-benzothiazol-3-yl)butan-1-ol Chemical compound C1=CC=C2C(CCCCO)=NSC2=C1 LNGXBZDOEJQTMR-UHFFFAOYSA-N 0.000 description 1
- AVCMPZUZKVCNNW-UHFFFAOYSA-N 4-(1,2-benzothiazol-3-yl)butanoic acid Chemical compound C1=CC=C2C(CCCC(=O)O)=NSC2=C1 AVCMPZUZKVCNNW-UHFFFAOYSA-N 0.000 description 1
- ZSMBCOAESGSKIP-UHFFFAOYSA-N 4-(1,2-benzoxazol-3-yl)butan-1-ol Chemical compound C1=CC=C2C(CCCCO)=NOC2=C1 ZSMBCOAESGSKIP-UHFFFAOYSA-N 0.000 description 1
- LBLSRDDHGILUJH-UHFFFAOYSA-N 4-(1h-indol-2-yl)butanoic acid Chemical compound C1=CC=C2NC(CCCC(=O)O)=CC2=C1 LBLSRDDHGILUJH-UHFFFAOYSA-N 0.000 description 1
- KMYSNUVWHIDKKC-UHFFFAOYSA-N 4-(4-fluorophenyl)-3-[4-[4-(4-fluorophenyl)piperidin-1-yl]butyl]-5-(trifluoromethyl)-2h-indazole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCC2=C3C(C=4C=CC(F)=CC=4)=C(C=CC3=NN2)C(F)(F)F)CC1 KMYSNUVWHIDKKC-UHFFFAOYSA-N 0.000 description 1
- OOENZYUWLSUCSP-UHFFFAOYSA-N 4-(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)butanenitrile Chemical compound FC1=CC=C2OCC(CCCC#N)C2=C1 OOENZYUWLSUCSP-UHFFFAOYSA-N 0.000 description 1
- ADTZOEMCRIMQDB-UHFFFAOYSA-N 4-(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)butanoyl chloride Chemical compound FC1=CC=C2OCC(CCCC(Cl)=O)C2=C1 ADTZOEMCRIMQDB-UHFFFAOYSA-N 0.000 description 1
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 1
- KZLXEOUFQIJXMZ-UHFFFAOYSA-N 4-[5-(trifluoromethyl)-2h-indazol-3-yl]butan-1-ol Chemical compound C1=C(C(F)(F)F)C=C2C(CCCCO)=NNC2=C1 KZLXEOUFQIJXMZ-UHFFFAOYSA-N 0.000 description 1
- HXAOUYGZEOZTJO-UHFFFAOYSA-N 4-chloro-1-(4-fluorophenyl)butan-1-one Chemical compound FC1=CC=C(C(=O)CCCCl)C=C1 HXAOUYGZEOZTJO-UHFFFAOYSA-N 0.000 description 1
- HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 description 1
- LDZLXQFDGRCELX-UHFFFAOYSA-N 4-phenylbutan-1-ol Chemical compound OCCCCC1=CC=CC=C1 LDZLXQFDGRCELX-UHFFFAOYSA-N 0.000 description 1
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical class C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 1
- CKLMHKQLDWEKRE-UHFFFAOYSA-N 5,6-dichloro-3-[4-[4-(4-fluorophenyl)piperidin-1-yl]butyl]-1h-indole Chemical compound C1=CC(F)=CC=C1C1CCN(CCCCC=2C3=CC(Cl)=C(Cl)C=C3NC=2)CC1 CKLMHKQLDWEKRE-UHFFFAOYSA-N 0.000 description 1
- VFCMERAHNNQMEN-UHFFFAOYSA-N 5-(1,2-benzoxazol-3-yl)pentane-1-sulfonic acid Chemical compound C1=CC=C2C(CCCCCS(=O)(=O)O)=NOC2=C1 VFCMERAHNNQMEN-UHFFFAOYSA-N 0.000 description 1
- XDJPAUBLMQOELC-UHFFFAOYSA-N 5-(1-methylsulfonylindol-3-yl)pentane-1-sulfonic acid Chemical compound C1=CC=C2N(S(=O)(=O)C)C=C(CCCCCS(O)(=O)=O)C2=C1 XDJPAUBLMQOELC-UHFFFAOYSA-N 0.000 description 1
- UCMPRXJVPNBKMP-UHFFFAOYSA-N 5-chloro-1-(4-fluorophenyl)-3-[2-[4-(4-fluorophenyl)piperidin-1-yl]ethoxy]indole Chemical compound C1=CC(F)=CC=C1C1CCN(CCOC=2C3=CC(Cl)=CC=C3N(C=3C=CC(F)=CC=3)C=2)CC1 UCMPRXJVPNBKMP-UHFFFAOYSA-N 0.000 description 1
- CNGNGGBYKPBLCU-UHFFFAOYSA-N 5-fluoro-1-benzofuran-3-carboxylic acid Chemical compound C1=C(F)C=C2C(C(=O)O)=COC2=C1 CNGNGGBYKPBLCU-UHFFFAOYSA-N 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229910000906 Bronze Inorganic materials 0.000 description 1
- KCDJLEUAFNDANQ-UHFFFAOYSA-N C1(=CC=CC=C1)CN1CCC2(CC1)OC=C1C(=C2)C=CC=C1 Chemical compound C1(=CC=CC=C1)CN1CCC2(CC1)OC=C1C(=C2)C=CC=C1 KCDJLEUAFNDANQ-UHFFFAOYSA-N 0.000 description 1
- DZPXXDUAQFAGFO-UHFFFAOYSA-N C1=CC=C2OCCC2=C1.C1=CC=C2OC=CC2=C1 Chemical compound C1=CC=C2OCCC2=C1.C1=CC=C2OC=CC2=C1 DZPXXDUAQFAGFO-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OCOMXEARNAZVBC-XBXARRHUSA-N OC1C(C2=CC=CC=C2C1)C/C=C/C(=O)OC Chemical compound OC1C(C2=CC=CC=C2C1)C/C=C/C(=O)OC OCOMXEARNAZVBC-XBXARRHUSA-N 0.000 description 1
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 229940122490 Sigma receptor antagonist Drugs 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241001533587 Spironucleus Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 238000006887 Ullmann reaction Methods 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- DDSZWBCJXDRQDU-UHFFFAOYSA-N [N].C1CCNCC1 Chemical group [N].C1CCNCC1 DDSZWBCJXDRQDU-UHFFFAOYSA-N 0.000 description 1
- 229950003769 acefylline Drugs 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003496 anti-amnesic effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000004802 benzothiophens Chemical class 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 239000010974 bronze Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- LFLBHTZRLVHUQC-UHFFFAOYSA-N butyl methanesulfonate Chemical compound CCCCOS(C)(=O)=O LFLBHTZRLVHUQC-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 201000002676 cerebral atherosclerosis Diseases 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 description 1
- 229940018557 citraconic acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- INGKGLJMYBPGKZ-UHFFFAOYSA-N dimethyl 2-[(5-fluoro-2,3-dihydro-1-benzofuran-3-yl)methyl]propanedioate Chemical compound C1=C(F)C=C2C(CC(C(=O)OC)C(=O)OC)COC2=C1 INGKGLJMYBPGKZ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- CCSYECWEHKBSRQ-UHFFFAOYSA-N ethyl 2-(1-benzothiophen-3-ylmethoxy)acetate Chemical compound C1=CC=C2C(COCC(=O)OCC)=CSC2=C1 CCSYECWEHKBSRQ-UHFFFAOYSA-N 0.000 description 1
- OISPPYAHNHQFSI-UHFFFAOYSA-N ethyl 3-[4-(4-fluorophenyl)piperidin-1-yl]propanoate Chemical compound C1CN(CCC(=O)OCC)CCC1C1=CC=C(F)C=C1 OISPPYAHNHQFSI-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000000556 factor analysis Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000000295 fuel oil Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 208000028326 generalized seizure Diseases 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- FGFUBBNNYLNVLJ-UHFFFAOYSA-N indolone Natural products C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 description 1
- 239000012155 injection solvent Substances 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical class C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- MLDCBJPLHBPJET-UHFFFAOYSA-N l-687,384 Chemical compound C1CC2(C3=CC=CC=C3CCC2)CCN1CC1=CC=CC=C1 MLDCBJPLHBPJET-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- OPUAWDUYWRUIIL-UHFFFAOYSA-N methanedisulfonic acid Chemical compound OS(=O)(=O)CS(O)(=O)=O OPUAWDUYWRUIIL-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- VKNXYAQLRDOEFK-UHFFFAOYSA-N methyl 2-(1,2-benzoxazol-3-yl)acetate Chemical compound C1=CC=C2C(CC(=O)OC)=NOC2=C1 VKNXYAQLRDOEFK-UHFFFAOYSA-N 0.000 description 1
- ODKSYEYDLVKYNI-UHFFFAOYSA-N methyl 2-(1-benzothiophen-3-yl)acetate Chemical compound C1=CC=C2C(CC(=O)OC)=CSC2=C1 ODKSYEYDLVKYNI-UHFFFAOYSA-N 0.000 description 1
- MSMYCGYVKSREQJ-UHFFFAOYSA-N methyl 3-(1,2-benzoxazol-3-yl)propanoate Chemical compound C1=CC=C2C(CCC(=O)OC)=NOC2=C1 MSMYCGYVKSREQJ-UHFFFAOYSA-N 0.000 description 1
- ZEJUFCOACOWDPP-UHFFFAOYSA-N methyl 4-(1h-indol-3-yl)butanoate Chemical compound C1=CC=C2C(CCCC(=O)OC)=CNC2=C1 ZEJUFCOACOWDPP-UHFFFAOYSA-N 0.000 description 1
- NNVYRRAPFAOSTL-UHFFFAOYSA-N methyl 5-chloro-3-(2-ethoxy-2-oxoethoxy)-1-(4-fluorophenyl)indole-2-carboxylate Chemical compound C12=CC=C(Cl)C=C2C(OCC(=O)OCC)=C(C(=O)OC)N1C1=CC=C(F)C=C1 NNVYRRAPFAOSTL-UHFFFAOYSA-N 0.000 description 1
- LRKHQYYRUOJNRW-UHFFFAOYSA-N methyl 5-fluoro-1-benzofuran-3-carboxylate Chemical compound C1=C(F)C=C2C(C(=O)OC)=COC2=C1 LRKHQYYRUOJNRW-UHFFFAOYSA-N 0.000 description 1
- ZOXRNCDTPJXOAI-UHFFFAOYSA-N methyl 5-fluoro-2,3-dihydro-1-benzofuran-3-carboxylate Chemical compound C1=C(F)C=C2C(C(=O)OC)COC2=C1 ZOXRNCDTPJXOAI-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- YRCHYHRCBXNYNU-UHFFFAOYSA-N n-[[3-fluoro-4-[2-[5-[(2-methoxyethylamino)methyl]pyridin-2-yl]thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-(4-fluorophenyl)acetamide Chemical compound N1=CC(CNCCOC)=CC=C1C1=CC2=NC=CC(OC=3C(=CC(NC(=S)NC(=O)CC=4C=CC(F)=CC=4)=CC=3)F)=C2S1 YRCHYHRCBXNYNU-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- XDMLFNJIGKRHPY-UHFFFAOYSA-N phenyl pentane-1-sulfonate Chemical compound CCCCCS(=O)(=O)OC1=CC=CC=C1 XDMLFNJIGKRHPY-UHFFFAOYSA-N 0.000 description 1
- SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical class C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960005335 propanol Drugs 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- ZBYFQSPEUIVDTF-UHFFFAOYSA-N spiro[1,2-dihydroindene-3,4'-piperidine] Chemical compound C12=CC=CC=C2CCC21CCNCC2 ZBYFQSPEUIVDTF-UHFFFAOYSA-N 0.000 description 1
- TWCBNOVLZABJAN-UHFFFAOYSA-N spiro[2,3-dihydrochromene-4,4'-piperidine] Chemical compound C1CNCCC21C1=CC=CC=C1OCC2 TWCBNOVLZABJAN-UHFFFAOYSA-N 0.000 description 1
- ZMSPWDUZXTYCQX-UHFFFAOYSA-N spiro[isochromene-3,4'-piperidine] Chemical compound C1CNCCC21C=C1C=CC=CC1=CO2 ZMSPWDUZXTYCQX-UHFFFAOYSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
- QQXLDOJGLXJCSE-KNVOCYPGSA-N tropinone Chemical compound C1C(=O)C[C@H]2CC[C@@H]1N2C QQXLDOJGLXJCSE-KNVOCYPGSA-N 0.000 description 1
- 238000011679 wistar WU rat Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Peptides Or Proteins (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK112991A DK112991D0 (da) | 1991-06-13 | 1991-06-13 | Carbocycliske eller heterocycliske forbindelser |
DK113191A DK113191D0 (da) | 1991-06-13 | 1991-06-13 | Spirocycliske forbindelser |
DK15792A DK15792D0 (da) | 1992-02-10 | 1992-02-10 | Spirocyclic compounds |
DK1131/91 | 1992-02-10 | ||
DK1129/91 | 1992-02-10 | ||
DK157/92 | 1992-02-10 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH06508360A JPH06508360A (ja) | 1994-09-22 |
JP2834577B2 true JP2834577B2 (ja) | 1998-12-09 |
Family
ID=27220471
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP5500747A Expired - Lifetime JP2834577B2 (ja) | 1991-06-13 | 1992-06-12 | 抗不安作用を有するピペリジン誘導体 |
JP10139146A Pending JPH111475A (ja) | 1991-06-13 | 1998-05-06 | 抗不安作用を有するピペリジン誘導体 |
JP13918398A Expired - Fee Related JP3203230B2 (ja) | 1991-06-13 | 1998-05-06 | 抗不安作用を有するピペリジン誘導体 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP10139146A Pending JPH111475A (ja) | 1991-06-13 | 1998-05-06 | 抗不安作用を有するピペリジン誘導体 |
JP13918398A Expired - Fee Related JP3203230B2 (ja) | 1991-06-13 | 1998-05-06 | 抗不安作用を有するピペリジン誘導体 |
Country Status (22)
Country | Link |
---|---|
US (4) | US5665725A (hu) |
EP (4) | EP0593511B1 (hu) |
JP (3) | JP2834577B2 (hu) |
KR (1) | KR100212231B1 (hu) |
AT (2) | ATE239022T1 (hu) |
AU (1) | AU664557B2 (hu) |
CA (1) | CA2111204C (hu) |
CZ (1) | CZ289479B6 (hu) |
DE (2) | DE69233038T2 (hu) |
DK (1) | DK0593511T3 (hu) |
ES (1) | ES2123557T3 (hu) |
FI (2) | FI108137B (hu) |
HK (1) | HK1009272A1 (hu) |
HU (1) | HU210869A9 (hu) |
IE (3) | IE990568A1 (hu) |
IL (1) | IL102155A0 (hu) |
NO (4) | NO934494D0 (hu) |
NZ (1) | NZ243065A (hu) |
RU (1) | RU2142952C1 (hu) |
SG (1) | SG48237A1 (hu) |
SK (3) | SK280899B6 (hu) |
WO (1) | WO1992022554A1 (hu) |
Families Citing this family (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW263504B (hu) * | 1991-10-03 | 1995-11-21 | Pfizer | |
GB9305641D0 (en) * | 1993-03-18 | 1993-05-05 | Merck Sharp & Dohme | Therapeutic agents |
EP0702681A1 (en) * | 1993-06-07 | 1996-03-27 | Merck & Co. Inc. | Spiro-substituted azacycles as neurokinin antagonists |
US5607936A (en) * | 1994-09-30 | 1997-03-04 | Merck & Co., Inc. | Substituted aryl piperazines as neurokinin antagonists |
GB9510459D0 (en) | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
US5654316A (en) * | 1995-06-06 | 1997-08-05 | Schering Corporation | Piperidine derivatives as neurokinin antagonists |
IL123583A (en) * | 1995-10-13 | 2003-07-31 | Neurosearch As | 3-substituted -8-azabicyclo [3,2,1] oct-2-ene derivatives, their preparation and pharmaceutical compositions containing them |
CZ287821B6 (en) * | 1996-05-13 | 2001-02-14 | Zeneca Ltd | Bicyclic amines, process of their preparation and insecticidal, acaricidal and nematocidal agent containing thereof |
WO1998008816A1 (fr) * | 1996-08-26 | 1998-03-05 | Meiji Seika Kaisha, Ltd. | Derives d'indoxyle et psychotropes |
GB9623944D0 (en) * | 1996-11-15 | 1997-01-08 | Zeneca Ltd | Bicyclic amine derivatives |
GB9624114D0 (en) * | 1996-11-20 | 1997-01-08 | Zeneca Ltd | Pesticidal bicyclic amine derivatives |
GB9624611D0 (en) | 1996-11-26 | 1997-01-15 | Zeneca Ltd | Bicyclic amine compounds |
NZ335422A (en) | 1996-11-26 | 2000-10-27 | Zeneca Ltd | 8-azabicyclo[3.2.1]octane-, 8-azabicyclo [3.2.1] oct-6-ene-, 9-azabicyclo[3.3.1]nonane-, 9-aza-3-oxabicyclo[3.3.1]nonane- and 9-aza-3-thiabicyclo[3.3.1]nonane derivatives for use in insecticides |
GB9704948D0 (en) * | 1997-03-11 | 1997-04-30 | Knoll Ag | Therapeutic agents |
US6376505B1 (en) | 1997-05-29 | 2002-04-23 | Eli Lilly And Company | 5-HT1A and 5-HT1Dαdalpha antagonists |
WO1998053823A1 (en) * | 1997-05-29 | 1998-12-03 | Eli Lilly And Company | 5-HT1A AND 5-HT1Dα ANTAGONISTS |
DE19725664A1 (de) | 1997-06-18 | 1998-12-24 | Merck Patent Gmbh | 3-Benzylpiperidine |
EA001728B1 (ru) | 1997-07-08 | 2001-08-27 | Х.Лундбекк А/С | Способ получения циталопрама |
UA64769C2 (uk) * | 1997-11-07 | 2004-03-15 | Х. Луннбек А/С | Гідрогалогеніди 1'-[4-[1-(4-фторофеніл)-1н-індол-3-іл]-1-бутил]-спіро[ізобензофуран-1(3н),4'-піперидину], фармацевтична композиція та спосіб лікування |
SK283907B6 (sk) | 1997-11-11 | 2004-04-06 | H. Lundbeck A/S | Spôsob výroby citalopramu a medziprodukty |
US6013652A (en) * | 1997-12-04 | 2000-01-11 | Merck & Co., Inc. | Spiro-substituted azacycles as neurokinin antagonists |
US6166209A (en) * | 1997-12-11 | 2000-12-26 | Hoffmann-La Roche Inc. | Piperidine derivatives |
EP1069899A1 (en) | 1998-04-07 | 2001-01-24 | H. Lundbeck A/S | Treatment of panic attacks |
PT1068184E (pt) * | 1998-04-08 | 2002-12-31 | Wyeth Corp | Derivados n-ariloxietilamina para o tratamento de depressao |
YU18701A (sh) | 1998-09-15 | 2003-07-07 | H. Lundbeck A/S. | Tretiranje depresije |
US6506378B1 (en) | 1998-12-16 | 2003-01-14 | Arch Development Corporation | Vesicular monoamine transporter gene therapy in Parkinson's disease |
TWI243173B (en) | 1999-11-17 | 2005-11-11 | Akzo Nobel Nv | Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives |
US7211594B2 (en) | 2000-07-31 | 2007-05-01 | Signal Pharmaceuticals, Llc | Indazole compounds and compositions thereof as JNK inhibitors and for the treatment of diseases associated therewith |
US6897231B2 (en) | 2000-07-31 | 2005-05-24 | Signal Pharmaceuticals, Inc. | Indazole derivatives as JNK inhibitors and compositions and methods related thereto |
JP4745491B2 (ja) * | 2000-10-11 | 2011-08-10 | 株式会社明治 | インドール長鎖アルコール及びこれを含有する医薬 |
US7429599B2 (en) | 2000-12-06 | 2008-09-30 | Signal Pharmaceuticals, Llc | Methods for treating or preventing an inflammatory or metabolic condition or inhibiting JNK |
AR035521A1 (es) * | 2000-12-22 | 2004-06-02 | Lundbeck & Co As H | Derivados de 3-indolina y composicion farmaceutica que los comprende |
US6713479B2 (en) | 2001-03-02 | 2004-03-30 | Sepracor Inc. | Piperidine-piperazine ligands for neurotransmitter receptors |
WO2002102387A1 (en) * | 2001-06-18 | 2002-12-27 | H. Lundbeck A/S | Treatment of neuropathic pain |
US20030078278A1 (en) * | 2001-06-26 | 2003-04-24 | Pfizer Inc. | Spiropiperidine compounds as ligands for ORL-1 receptor |
US6727264B1 (en) | 2001-07-05 | 2004-04-27 | Synaptic Pharmaceutical Corporation | Substituted anilinic piperidines as MCH selective antagonists |
DE10153346A1 (de) | 2001-10-29 | 2004-04-22 | Grünenthal GmbH | Substituierte Indole |
US7407983B2 (en) | 2002-02-13 | 2008-08-05 | Meiji Dairies Corporation | Indole derivatives substituted with long-chain alcohols and medicaments containing them |
AU2003217961B2 (en) | 2002-03-08 | 2008-02-28 | Signal Pharmaceuticals, Llc | Combination therapy for treating, preventing or managing proliferative disorders and cancers |
WO2004026855A1 (en) * | 2002-09-20 | 2004-04-01 | H. Lundbeck A/S | Method for manufacture of dihydroisobenzofuran derivatives |
JP2006511500A (ja) * | 2002-10-30 | 2006-04-06 | メルク エンド カムパニー インコーポレーテッド | γ−アミノアミド系のケモカイン受容体活性調節剤 |
JP4390712B2 (ja) * | 2003-03-31 | 2009-12-24 | ピレリ・アンド・チ・ソチエタ・ペル・アツィオーニ | 細分割形態の加硫ゴムを含む熱可塑性材料 |
US20060052386A1 (en) * | 2003-06-12 | 2006-03-09 | Tadeusz Wieloch | Sigma ligands for neuronal regeneration and functional recovery |
WO2004110388A2 (en) * | 2003-06-12 | 2004-12-23 | Agy Therapeutics, Inc. | Sigma ligands for neuronal regeneration and functional recovery |
US7008953B2 (en) | 2003-07-30 | 2006-03-07 | Agouron Pharmaceuticals, Inc. | 3, 5 Disubstituted indazole compounds, pharmaceutical compositions, and methods for mediating or inhibiting cell proliferation |
US7786141B2 (en) * | 2004-08-19 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Dihydrospiroindene modulators of muscarinic receptors |
RU2007109794A (ru) * | 2004-08-19 | 2008-09-27 | Вертекс Фармасьютикалз, Инкорпорейтед (Us) | Модуляторы мускариновых рецепторов |
EP1634873A1 (en) | 2004-08-27 | 2006-03-15 | Laboratorios Del Dr. Esteve, S.A. | Sigma receptor inhibitors |
BRPI0514736A (pt) | 2004-08-27 | 2008-06-24 | Esteve Labor Dr | inibidores do receptor sigma |
MX2007002341A (es) | 2004-08-27 | 2007-09-25 | Esteve Labor Dr | Inhibidores del receptor sigma. |
EP1634872A1 (en) * | 2004-08-27 | 2006-03-15 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
JP5139061B2 (ja) | 2004-08-27 | 2013-02-06 | ラボラトリオス デル ドクトール エステベ エセ.ア. | シグマ受容体阻害剤 |
AU2005309365B2 (en) * | 2004-11-29 | 2011-10-06 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP1943250A1 (en) * | 2005-09-09 | 2008-07-16 | Euro-Celtique S.A. | Fused and spirocycle compounds and the use thereof |
EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
US20070112017A1 (en) | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
WO2007063385A2 (en) * | 2005-12-01 | 2007-06-07 | Pfizer Products Inc. | Spirocyclic amine histamine-3 receptor antagonists |
AU2006330866A1 (en) | 2005-12-22 | 2007-07-05 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
ATE517106T1 (de) * | 2006-02-22 | 2011-08-15 | Vertex Pharma | Kondensierte spiropiperidine als modulatoren muskarinartiger rezeptoren |
EP1988892A2 (en) | 2006-02-22 | 2008-11-12 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP1829875A1 (en) | 2006-03-01 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
WO2007098953A1 (en) * | 2006-03-01 | 2007-09-07 | Laboratorios Del Dr. Esteve, S.A. | Pyrazole derivatives as sigma receptor inhibitors |
EP1829866A1 (en) * | 2006-03-02 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | Sigma receptor inhibitors |
EP1829867A1 (en) | 2006-03-03 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | Imidazole compounds having pharmaceutical activity towards the sigma receptor |
US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
MX2008014320A (es) | 2006-05-09 | 2009-03-25 | Braincells Inc | Neurogenesis mediada por el receptor de 5-hidroxitriptamina. |
AU2007249399A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
CN101500565A (zh) | 2006-06-29 | 2009-08-05 | 弗特克斯药品有限公司 | 毒蕈碱性受体的调节剂 |
CN101553231A (zh) | 2006-08-15 | 2009-10-07 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
JP2010501561A (ja) * | 2006-08-18 | 2010-01-21 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体の調節剤 |
JP2010502722A (ja) | 2006-09-08 | 2010-01-28 | ブレインセルス,インコーポレイティド | 4−アシルアミノピリジン誘導体を含む組み合わせ |
US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
US20080146107A1 (en) * | 2006-12-05 | 2008-06-19 | Interwrap Inc. | Stretchable scrim wrapping material |
PE20081559A1 (es) | 2007-01-12 | 2008-11-20 | Merck & Co Inc | DERIVADOS DE ESPIROCROMANONA SUSTITUIDOS COMO INHIBIDORES DE ACETIL CoA CARBOXILASA |
AU2008205642B2 (en) | 2007-01-12 | 2013-06-06 | Msd K.K. | Spirochromanon derivatives |
CL2008000070A1 (es) * | 2007-01-17 | 2008-07-25 | Lg Life Sciences Ltd | Monosal del acido maleico (3-[({1-[(2-amino-9h-purin-9-il)metil]ciclopropil}oxi)metil]-8,8-dimetil-3,7-dioxo-2,4,6-trioxa-3 lambda 5-fosfanon-1-il-pivalato; composicion farmaceutica que comprende a dicha monosal; y uso para el tratamiento del virus h |
CA2700724A1 (en) * | 2007-10-03 | 2009-04-09 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP2116539A1 (en) | 2008-04-25 | 2009-11-11 | Laboratorios Del. Dr. Esteve, S.A. | 1-aryl-3-aminoalkoxy-pyrazoles as sigma ligands enhancing analgesic effects of opioids and attenuating the dependency thereof |
WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
RU2641648C1 (ru) | 2009-12-04 | 2018-01-19 | Суновион Фармасьютикалз, Инк. | Полициклические соединения и способы их применения |
EP2353598A1 (en) | 2010-02-04 | 2011-08-10 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for use in the prevention and/or treatment of postoperative pain |
EP2353591A1 (en) | 2010-02-04 | 2011-08-10 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for potentiating the analgesic effect of opioids and opiates in post-operative pain and attenuating the dependency thereof |
AR080133A1 (es) * | 2010-02-04 | 2012-03-14 | Esteve Labor Dr | Clorhidrato de 4-(-2-((5-metil-1-(2-naftalenil)-1h-pirazol-3-il)oxi)etil)morfolina y formas cristalinas del mismo |
KR20120123089A (ko) * | 2010-02-16 | 2012-11-07 | 화이자 인코포레이티드 | 5-HT₄ 수용체의 부분 효능제인 (R)-4-((4-((4-(테트라히드로푸란-3-일옥시)벤조[d]이속사졸-3-일옥시)메틸)피페리딘-1-일)메틸)테트라히드로-2H-피란-4-올 |
EP2388005A1 (en) | 2010-05-21 | 2011-11-23 | Laboratorios Del. Dr. Esteve, S.A. | Sigma ligands for the prevention and/or treatment of emesis induced by chemotherapy or radiotherapy |
EP2395003A1 (en) | 2010-05-27 | 2011-12-14 | Laboratorios Del. Dr. Esteve, S.A. | Pyrazole compounds as sigma receptor inhibitors |
EP2415471A1 (en) | 2010-08-03 | 2012-02-08 | Laboratorios Del. Dr. Esteve, S.A. | Use of sigma ligands in opioid-induced hyperalgesia |
EP2524694A1 (en) | 2011-05-19 | 2012-11-21 | Laboratorios Del. Dr. Esteve, S.A. | Use of sigma ligands in diabetes type-2 associated pain |
US20130333095A1 (en) * | 2012-06-14 | 2013-12-19 | Michael Dudick | Cap with cap replacement section |
TW201607538A (zh) | 2013-12-17 | 2016-03-01 | 以斯提夫博士實驗室股份有限公司 | 血清素-去甲腎上腺素再攝取抑制劑(SNRIS)和σ受體配體組合物 |
GB201511382D0 (en) | 2015-06-29 | 2015-08-12 | Imp Innovations Ltd | Novel compounds and their use in therapy |
PT3413870T (pt) | 2016-02-11 | 2021-09-10 | Sigmathera Sas | Igmesina para utilização no tratamento de doença de alzheimer |
RU2691454C2 (ru) * | 2016-03-30 | 2019-06-14 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт фармакологии имени В.В. Закусова" | Использование 3,4,5-триметокси-N'(2,2,6,6-тетраметил-пиперидин-4-илиден)бензогидразида гидрохлорида в качестве анксиолитического средства |
KR20190065246A (ko) | 2016-07-29 | 2019-06-11 | 선오비온 파마슈티컬스 인코포레이티드 | 화합물 및 조성물 및 이들의 용도 |
CN116283877A (zh) | 2016-07-29 | 2023-06-23 | 赛诺维信制药公司 | 化合物、组合物及其用途 |
MX2019009763A (es) | 2017-02-16 | 2019-11-21 | Sunovion Pharmaceuticals Inc | Metodos para tratar esquizofrenia. |
SG11202000669VA (en) | 2017-08-02 | 2020-02-27 | Sunovion Pharmaceuticals Inc | Isochroman compounds and uses thereof |
WO2019161238A1 (en) | 2018-02-16 | 2019-08-22 | Sunovion Pharmaceuticals Inc. | Salts, crystal forms, and production methods thereof |
AU2020236225A1 (en) | 2019-03-14 | 2021-09-16 | Sunovion Pharmaceuticals Inc. | Salts of a isochromanyl compound and crystalline forms, processes for preparing, therapeutic uses, and pharmaceutical compositions thereof |
KR20230003503A (ko) | 2020-04-14 | 2023-01-06 | 선오비온 파마슈티컬스 인코포레이티드 | 신경학적 및 정신의학적 장애의 치료를 위한 (S)-(4,5-디히드로-7H-티에노[2,3-c]피란-7-일)-N-메틸메탄아민 |
JP2023526515A (ja) | 2020-05-20 | 2023-06-21 | ザ ボード オブ トラスティーズ オブ ザ ユニヴァーシティ オブ イリノイ | リソソーム蓄積症をヒスタチンペプチドで処置するための方法 |
Family Cites Families (80)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2891066A (en) * | 1957-08-14 | 1959-06-16 | Parke Davis & Co | 4,o-substituted phenyl 1 alkanol piperidines and esters thereof |
GB944443A (hu) * | 1959-09-25 | 1900-01-01 | ||
FR1335831A (fr) * | 1962-10-09 | 1963-08-23 | Res Lab Dr C Janssen Nv | Procédé de préparation de nu-(3, 3-diphényl-3-alcanoyl)-propylspiro |
US3408356A (en) * | 1965-08-31 | 1968-10-29 | Squibb & Sons Inc | Long chain esters of 4'-fluoro-4-[4-hydroxy-4-(alpha, alpha, alpha-trifluorotolyl)piperi-dino]butyrophenone and the like |
GB1154976A (en) * | 1967-02-21 | 1969-06-11 | Pfizer Ltd | N-Phenyl Indoline Derivatives |
US3476760A (en) * | 1967-03-06 | 1969-11-04 | Smithkline Corp | Substituted piperidinoalkylthianaphthenes and benzofurans |
US3654287A (en) * | 1970-08-26 | 1972-04-04 | Mead Johnson & Co | Spiroindanylpiperidines |
US3686213A (en) * | 1970-08-28 | 1972-08-22 | American Cyanamid Co | Substituted aminoethyl indoles |
US3686186A (en) * | 1970-10-05 | 1972-08-22 | William J Houlihan | Substituted isochroman or phthalan piperidenes |
US3745165A (en) * | 1970-10-05 | 1973-07-10 | Sandoz Ag | Substituted isochroman or phthalan piperidenes |
US4021451A (en) * | 1972-05-16 | 1977-05-03 | American Home Products Corporation | Process for preparing polycyclic heterocycles having a pyran ring |
DE2322470A1 (de) * | 1973-05-04 | 1974-11-21 | Boehringer Sohn Ingelheim | Neue indolyl-piperidino-(bzw. 1,2,5,6tetrahydro-pyridyl-)butyrophenone und verfahren zu ihrer herstellung |
GB1469108A (en) * | 1973-06-25 | 1977-03-30 | Kefalas As | Thiaxanthene derivative |
US4038395A (en) * | 1973-06-25 | 1977-07-26 | Kefalas A/S | Compositions of and method of treating with the alpha-isomer of 2-chloro-9-[3'-(N'-2-hydroxyethylpiperazino-N)-propylidene]-thiaxanthene, carboxylic acid esters thereof and acid addition salts of these compounds |
US3962259A (en) * | 1973-12-12 | 1976-06-08 | American Hoechst Corporation | 1,3-Dihydrospiro[isobenzofuran]s and derivatives thereof |
FR2258843B1 (hu) * | 1974-01-30 | 1977-09-09 | Roussel Uclaf | |
DE2433769A1 (de) | 1974-07-13 | 1976-01-22 | Seelemann Baumann Gmbh | Vorreisserwalze fuer open-end spinnmaschinen |
US3936464A (en) * | 1974-10-25 | 1976-02-03 | American Cyanamid Company | 1-Acyl-3-[2-(4-phenyl-1-piperidinyl)ethyl]indolines |
IL48508A (en) * | 1974-12-09 | 1979-10-31 | Roussel Uclaf | Pharmaceutical compositions comprising piperidylindole derivatives |
FR2354766A1 (fr) * | 1976-06-17 | 1978-01-13 | Labaz | Derives n-aminoalkyles d'indole et procedes pour les preparer |
FR2362628A1 (fr) * | 1976-08-26 | 1978-03-24 | Roussel Uclaf | Nouveaux derives du piperidyl-indole et leurs sels, procede de preparation et application a titre de medicaments |
FR2421900A1 (fr) * | 1977-03-17 | 1979-11-02 | Sauba Lab | Piperazino-3-indoles, leur procede de preparation et leurs applications therapeutiques |
FR2391211A2 (fr) * | 1977-05-18 | 1978-12-15 | Roussel Uclaf | Nouveaux derives de 2,3-dihydroa(4-(3-indolyl) 1-piperidinyl) methyl 1,4-benzodioxin-2-methanol, un procede de preparation, et leur application comme medicaments |
GB1587961A (en) | 1977-10-11 | 1981-04-15 | Eadie Bros & Co Ltd | Card-clothing |
EG13536A (en) * | 1977-12-02 | 1981-12-31 | Hoechst Ag | Substituted 1,3-dihydrospiro(benzo(c)thiophene)s |
US4166119A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines |
EP0007399B1 (de) * | 1978-06-24 | 1982-01-20 | MERCK PATENT GmbH | Indolalkylamine, diese enthaltende pharmazeutische Zubereitungen und Verfahren zu ihrer Herstellung |
DE2827874A1 (de) * | 1978-06-24 | 1980-02-07 | Merck Patent Gmbh | Indolalkylamine und verfahren zu ihrer herstellung |
US4208417A (en) * | 1978-06-29 | 1980-06-17 | Pharmindustrie | Indole derivatives and their use as anxiolytics |
JPS55139381A (en) * | 1979-04-13 | 1980-10-31 | Dai Ichi Seiyaku Co Ltd | Spiroisochroman |
JPS55143980A (en) * | 1979-04-27 | 1980-11-10 | Dai Ichi Seiyaku Co Ltd | Anti-allergic preparation |
SE8004129L (sv) * | 1979-07-13 | 1981-01-14 | Roussel Uclaf | Nya tetrahydropyridin-4-yl-indolderivat samt salter derav, framstellning och anvendning derav sasom lekemedel samt kompositioner innehallande dessa foreningar |
NZ196284A (en) * | 1980-02-29 | 1983-12-16 | Kefalas As | 1-piperazino-3-phenylindane derivatives:pharmaceutical compositions |
US4358456A (en) * | 1980-05-03 | 1982-11-09 | John Wyeth & Brother Limited | Antipsychotic piperidinomethyl-indole derivatives |
US4302589A (en) * | 1980-05-08 | 1981-11-24 | American Cyanamid Company | Cis-mono and disubstituted-2-methyl-3-[(piperazinyl) and (piperidino)ethyl]indolines, intermediates for their preparation and methods of preparation |
EP0149229B1 (en) * | 1981-04-27 | 1989-06-14 | Hoechst-Roussel Pharmaceuticals Incorporated | 3-(gamma-chloropropyl)-6-fluor-1,2-benzisoxazole, process for its preparation and its use as an intermediate |
EP0077607A1 (en) * | 1981-09-17 | 1983-04-27 | Beecham Group Plc | N-substituted 3-aryl piperidines and derivatives thereof |
US4524207A (en) * | 1981-10-20 | 1985-06-18 | Hoechst-Roussel Pharmaceuticals Inc. | Process for preparing substituted 1,3-dihydrospiro[benzo(c)thiophene]s |
US4591586A (en) * | 1982-04-09 | 1986-05-27 | Hoechst-Roussel Pharmaceuticals | 6-fluoro-3-[3-(1-heterocyclo)propyl]-1,2-benzisoxazoles for treatment of pain, hypertension and psychoses |
US4420485A (en) * | 1982-09-29 | 1983-12-13 | Hoechst-Roussel Pharmaceuticals Inc. | 1'-[3-(1,2-Benzisoxazol-3-yl) proply]spiro[benzofuran-2(3H),3' or 4'-piperidines or 3'-pyrrolidines] |
FR2533924A1 (fr) * | 1982-10-05 | 1984-04-06 | Roussel Uclaf | Nouveaux derives du 4-(1h-indol-3-yl)a-methyl piperidine-1-ethanol, leurs sels, le procede de preparation, l'application a titre de medicaments et les compositions les renfermant |
IE55972B1 (en) * | 1982-10-07 | 1991-03-13 | Kefalas As | Phenylindene derivatives,acid addition salts thereof,and methods of preparation |
US4670447A (en) * | 1983-08-22 | 1987-06-02 | Hoechst-Roussel Pharmaceuticals Inc. | Antipsychotic 3-(piperidinyl)- and 3-(pyrrolidinyl)-1H-indazoles |
HU198036B (en) * | 1983-08-22 | 1989-07-28 | Hoechst Roussel Pharma | Process for production of derivatives of 3-piperidil-/1h/-indasole and medical preparatives containing them |
US4853470A (en) * | 1983-08-22 | 1989-08-01 | Hoechst-Roussel Pharmaceuticals, Inc. | 3-(piperidinyl)- and 3-(pyrrolidinyl)-1H-indazoles |
US4452802A (en) * | 1983-08-25 | 1984-06-05 | Hoechst-Roussel Pharmaceuticals Incorporated | Antihypertensive spiro[benzofuran-azalkanes] |
GB8422924D0 (en) * | 1984-09-11 | 1984-10-17 | Wyeth John & Brother Ltd | Prevention of hypertension |
GB8427125D0 (en) * | 1984-10-26 | 1984-12-05 | Lundbeck & Co As H | Organic compounds |
EP0367298B1 (en) * | 1985-02-28 | 1992-07-22 | Symbol Technologies, Inc. | Portable laser diode scanning head |
DE3509333A1 (de) * | 1985-03-15 | 1986-09-18 | Hoechst Ag, 6230 Frankfurt | Substituierte benzimidazolderivate, verfahren zu ihrer herstellung, sie enthaltende pharmazeutische zubereitungen und ihre verwendung als magensaeuresekretionshemmer |
IE58370B1 (en) * | 1985-04-10 | 1993-09-08 | Lundbeck & Co As H | Indole derivatives |
DE3521761A1 (de) * | 1985-06-19 | 1987-01-02 | Bayer Ag | Neue 1,4-dihydropyridine, verfahren zur herstellung und ihre verwendung in arzneimitteln |
US4742057A (en) * | 1985-12-05 | 1988-05-03 | Fujisawa Pharmaceutical Co., Ltd. | Antiallergic thiazole compounds |
DE3630903A1 (de) * | 1986-09-11 | 1988-03-24 | Thomae Gmbh Dr K | Neue tetrahydronaphthalin- und indanderivate, verfahren zu deren herstellung sowie diese enthaltende arzneimittel |
GB8628644D0 (en) * | 1986-12-01 | 1987-01-07 | Lunbeck A S H | Intermediates |
GB8704572D0 (en) * | 1987-02-26 | 1987-04-01 | Lundbeck & Co As H | Organic compounds |
MX173362B (es) * | 1987-03-02 | 1994-02-23 | Pfizer | Compuestos de piperazinil heterociclicos y procedimiento para su preparacion |
EP0302423A3 (en) * | 1987-08-07 | 1991-01-09 | Hoechst-Roussel Pharmaceuticals Incorporated | 1-phenyl-3-(1-piperazinyl)-1h-indazoles, a process and intermediates for their preparation, and the use thereof as medicaments |
PT88255B (pt) * | 1987-08-13 | 1995-03-01 | Glaxo Group Ltd | Processo para a preparacao de derivados do indole |
US4831031A (en) * | 1988-01-22 | 1989-05-16 | Pfizer Inc. | Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity |
FR2640266B2 (fr) * | 1988-07-12 | 1992-07-10 | Synthelabo | Derives de (hydroxy-1 piperidinyl-2 alkyl) indolones-2, quinoleinones-2, benzo(b)azepinones-2 et benzimidazolones-2, leur preparation et leur application en therapeutique |
GB8819024D0 (en) * | 1988-08-10 | 1988-09-14 | Glaxo Group Ltd | Chemical compounds |
WO1990006303A1 (en) * | 1988-12-02 | 1990-06-14 | Pfizer Inc. | Arylpiperidine derivatives |
GB8830312D0 (en) * | 1988-12-28 | 1989-02-22 | Lundbeck & Co As H | Heterocyclic compounds |
GB8908085D0 (en) * | 1989-04-11 | 1989-05-24 | Lundbeck & Co As H | New therapeutic use |
DE69011859T2 (de) * | 1989-05-02 | 1994-12-15 | Oregon State | Verwendung von sigma-rezeptor-liganden zur herstellung eines anxiolytikums. |
SE8901889D0 (sv) * | 1989-05-26 | 1989-05-26 | Astra Ab | Novel 8-substituted-2-aminotetralines |
GB8917069D0 (en) * | 1989-07-26 | 1989-09-13 | Merck Sharp & Dohme | Therapeutic agents |
US5109002A (en) * | 1989-09-08 | 1992-04-28 | Du Pont Merck Pharmaceutical Company | Antipsychotic 1-cycloalkylpiperidines |
CA2031663A1 (en) | 1989-12-07 | 1991-06-08 | Edwin Harm Roos | Material separation |
IL96507A0 (en) * | 1989-12-08 | 1991-08-16 | Merck & Co Inc | Nitrogen-containing spirocycles and pharmaceutical compositions containing them |
FR2662696A2 (fr) * | 1989-12-13 | 1991-12-06 | Rhone Poulenc Sante | Antagonistes de la serotonine, leur preparation et medicaments les contenant. |
EP0507863A4 (en) * | 1989-12-28 | 1993-07-07 | Virginia Commonwealth University | Sigma receptor ligands and the use thereof |
EP0445974A3 (en) * | 1990-03-05 | 1992-04-29 | Merck Sharp & Dohme Ltd. | Spirocyclic antipsychotic agents |
DK152090D0 (da) * | 1990-06-22 | 1990-06-22 | Lundbaek A S H | Piperidylsubstituerede indolderivater |
DK158590D0 (da) * | 1990-07-02 | 1990-07-02 | Lundbeck & Co As H | Indolderivater |
DK181190D0 (da) * | 1990-07-30 | 1990-07-30 | Lundbeck & Co As H | 3-aryl-indol- eller 3-aryl-indazolderivater |
DK238190D0 (da) * | 1990-10-03 | 1990-10-03 | Lundbeck & Co As H | Depotderivater |
DK286990D0 (da) * | 1990-12-04 | 1990-12-04 | Lundbeck & Co As H | Indanderivater |
GB9501222D0 (en) | 1995-01-21 | 1995-03-15 | English Card Clothing The Comp | Card-clothing wire |
-
1992
- 1992-06-08 NZ NZ243065A patent/NZ243065A/en not_active IP Right Cessation
- 1992-06-10 IL IL102155A patent/IL102155A0/xx not_active IP Right Cessation
- 1992-06-12 EP EP92912044A patent/EP0593511B1/en not_active Expired - Lifetime
- 1992-06-12 SK SK1409-93A patent/SK280899B6/sk not_active IP Right Cessation
- 1992-06-12 EP EP98101728A patent/EP0853085A1/en not_active Withdrawn
- 1992-06-12 SG SG1996008163A patent/SG48237A1/en unknown
- 1992-06-12 CA CA002111204A patent/CA2111204C/en not_active Expired - Fee Related
- 1992-06-12 EP EP98101729A patent/EP0859004B1/en not_active Expired - Lifetime
- 1992-06-12 SK SK1004-99A patent/SK281747B6/sk not_active IP Right Cessation
- 1992-06-12 KR KR1019930703860A patent/KR100212231B1/ko not_active IP Right Cessation
- 1992-06-12 RU RU93058600A patent/RU2142952C1/ru not_active IP Right Cessation
- 1992-06-12 DK DK92912044T patent/DK0593511T3/da active
- 1992-06-12 SK SK1005-99A patent/SK281748B6/sk not_active IP Right Cessation
- 1992-06-12 AT AT98101729T patent/ATE239022T1/de not_active IP Right Cessation
- 1992-06-12 DE DE69233038T patent/DE69233038T2/de not_active Expired - Fee Related
- 1992-06-12 CZ CZ19932726A patent/CZ289479B6/cs not_active IP Right Cessation
- 1992-06-12 AU AU19848/92A patent/AU664557B2/en not_active Ceased
- 1992-06-12 AT AT92912044T patent/ATE170523T1/de not_active IP Right Cessation
- 1992-06-12 ES ES92912044T patent/ES2123557T3/es not_active Expired - Lifetime
- 1992-06-12 EP EP92610044A patent/EP0518805A1/en active Pending
- 1992-06-12 WO PCT/DK1992/000183 patent/WO1992022554A1/en active IP Right Grant
- 1992-06-12 JP JP5500747A patent/JP2834577B2/ja not_active Expired - Lifetime
- 1992-06-12 DE DE69226867T patent/DE69226867T2/de not_active Expired - Fee Related
- 1992-07-01 IE IE19990568A patent/IE990568A1/en not_active IP Right Cessation
- 1992-07-01 IE IE188292A patent/IE921882A1/en not_active IP Right Cessation
- 1992-07-01 IE IE19990567A patent/IE990567A1/en not_active IP Right Cessation
-
1993
- 1993-12-09 NO NO934494D patent/NO934494D0/no unknown
- 1993-12-09 NO NO934494A patent/NO306497B1/no not_active IP Right Cessation
- 1993-12-10 FI FI935558A patent/FI108137B/fi active
- 1993-12-13 US US08/166,647 patent/US5665725A/en not_active Expired - Lifetime
-
1995
- 1995-03-30 HU HU95P/P00094P patent/HU210869A9/hu unknown
- 1995-06-07 US US08/478,563 patent/US5807871A/en not_active Expired - Fee Related
- 1995-06-07 US US08/486,510 patent/US6031099A/en not_active Expired - Fee Related
-
1998
- 1998-05-06 JP JP10139146A patent/JPH111475A/ja active Pending
- 1998-05-06 JP JP13918398A patent/JP3203230B2/ja not_active Expired - Fee Related
- 1998-08-12 HK HK98109879A patent/HK1009272A1/xx not_active IP Right Cessation
-
1999
- 1999-09-07 US US09/391,290 patent/US6207677B1/en not_active Expired - Fee Related
- 1999-09-16 NO NO19994488A patent/NO310275B1/no not_active IP Right Cessation
- 1999-09-16 NO NO994487A patent/NO994487D0/no not_active Application Discontinuation
- 1999-10-04 FI FI992135A patent/FI112480B/fi active
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2834577B2 (ja) | 抗不安作用を有するピペリジン誘導体 | |
JPH10512861A (ja) | セロトニン関連システムに対する効果を有する化合物 | |
WO2004041161A2 (en) | Tetrahydropyranyl cyclopentyl benzylamide modulators of chemokine receptor activity | |
JP2007517014A (ja) | N−置換ピペリジン及びピペラジン誘導体 | |
RU2156249C2 (ru) | Соединения фенилиндола | |
JP3308507B2 (ja) | スピロ〔ピペリジン−4,1′−ピロロ〔3,4−c〕ピロール〕 | |
JP4590102B2 (ja) | 医薬としての三環性δ3−ピペリジン類 | |
JP2001058989A (ja) | ピリミジン誘導体およびその塩 | |
CA2296901C (en) | Piperidine derivates having anxiolytic effect | |
JPH09202784A (ja) | 薬学的化合物 |